Corticotrophin-releasing hormone type 1 receptor gene (CRHR1) variants predict posttraumatic stress disorder onset and course in pediatric injury patients.
Corticotrophin-releasing hormone type 1 receptor gene (CRHR1) variants predict posttraumatic stress disorder onset and course in pediatric injury patients.
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DOI：
10.3233/dma-2011-0761
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Koenen KC
中科院分区：
文献类型：
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作者：
Amstadter AB;Nugent NR;Yang BZ;Miller A;Siburian R;Moorjani P;Haddad S;Basu A;Fagerness J;Saxe G;Smoller JW;Koenen KC
创伤后应激障碍（PTSD）是一种常见的致残焦虑症，可能发生在暴露于潜在的创伤性生活事件之后。创伤后应激障碍具有中度遗传性，但很少有特定的分子变异被确定为这种遗传性。调节下丘脑-垂体-肾上腺（HPA）轴的基因，如促肾上腺皮质激素释放激素1型受体基因（CRHR1），已被认为与创伤应激相关的表型有关，但与创伤后应激障碍的关系尚未得到研究。本研究旨在通过一项前瞻性研究，探讨CRHR1基因中9个单核苷酸多态性（SNPs）与创伤后应激症状之间的关系，该研究对103名儿童损伤患者（n = 103）进行了首次评估，这些患者是在医院的急性损伤后进行的。结果显示，在单变量水平上，多个snp与急性PTSD症状相关，经多重检验校正后，rs12944712与急性PTSD症状显著相关。纵向潜在生长曲线分析表明rs12944712也与急性症状水平和症状随时间的发展轨迹有关。本研究进一步支持了CRHR1在青少年潜在创伤性事件暴露后的应激反应中的作用。需要注意的是，本研究样本量较小，因此统计效力较低；接下来，本研究的结果应该被认为是初步的。虽然结果不是决定性的，但这项研究的发现保证了未来关于该基因变异如何与青少年创伤性事件暴露反应相关的复制研究。
Posttraumatic stress disorder (PTSD) is a common and disabling anxiety disorder that may occur in the aftermath of exposure to potentially traumatic life events. PTSD is moderately heritable, but few specific molecular variants accounting for this heritability have been identified. Genes regulating the hypothalamic-pituitary-adrenal (HPA) axis, such as corticotrophin-releasing hormone type 1 receptor gene (CRHR1), have been implicated in traumatic-stress related phenotypes but have yet to be studied in relation to PTSD. The present study sought to examine the relation between 9 single nucleotide polymorphisms (SNPs) in the CRHR1 gene and posttraumatic stress symptoms in a prospective study of pediatric injury patients (n = 103) who were first assessed in the acute aftermath of their injury at the hospital. Results indicated that multiple SNPs were associated with acute symptoms at a univariate level, and after correction for multiple testing, rs12944712 was significantly related to acute PTSD symptoms. Longitudinal latent growth curve analyses suggest that rs12944712 is also related to both acute symptom level and trajectory of symptoms over time. The present study adds support for the role of CRHR1 in the stress response following potentially traumatic event exposure in youth. It should be noted that the sample size in this study was small, and therefore statistical power was low; following, results from this study should be considered preliminary. Although results are not definitive, the findings from this study warrant future replication studies on how variation in this gene relates to response to traumatic event exposure in youth.